tbuckley/cabot-search huggingface dataset:
Abstract 12171: Cardiovascular Events in Chimeric Antigen Receptor T-Cell Therapy Recipients With Pre-Existing Cardiac Dysfunction
Authors: Stephen Sansoterra, Michael Rothberg, Peter Riedell, Mahin Rehman, Richard Steingart, Eric H Yang, Daria Gaut, Thomas Althaus, Roni Shouval, Adam Gold, Miguel-Angel Perales, Mark Geyer, Jae Park, Maria Lia Palomba, Stephanie Feldman, Elena Mead, Jennifer Liu, Carol Chen, Dipti Gupta, Anthony Yu, Kristine Jang, Lauren Balkan, Tarek Barbar, Katherine Lee Chuy, Bhisham Harchandani, Evelyn M Horn, Maria G Karas, Irina Sobol, John Leonard, Koen van Besien, Matthew Frigault, Gaurav Shah, Tomas G Neilan, Syed S Mahmood
Journal: Circulation (2022)

Introduction: Cytokine release syndrome (CRS) and associated cardiovascular (CV) events are common following infusion of chimeric antigen receptor T cell therapy (CAR-T). There are no data characterizing whether CAR-T recipients with a pre-existing cardiac dysfunction (LVEF &lt;53%) are at increased risk for CV events following CAR-T. Hypothesis: We hypothesized that cardiac dysfunction would be associated with a higher rate of CV events following CAR-T infusion. CV events were defined as a composite of cardiogenic shock, clinical heart failure, myocardial infarction, or arrhythmia. Methods: Patients in a multi-center registry of adult CAR-T recipients with a known baseline LVEF were included (n=241). Covariates included standard baseline CV and cancer parameters. Results: In total, 22 (9%) CAR-T patients had a pre-existing cardiac dysfunction. Those with and without [219 (91%)] baseline cardiac dysfunction were similar in age, gender, pre-existing CV risk factors, and ECOG performance status. LVEF among patients with cardiac dysfunction ranged from 25%-52%. There was no difference in prior anthracycline use, cancer type or burden, but cardiac dysfunction patients had higher rates of prior radiation (36% vs 16%, p=0.02). Cardiac dysfunction patients received less investigational CAR-T (9% vs 31%, p=0.03), more tisagenlecleucel (36% vs 18%, p=0.04), and had similar rates of axicabtagene ciloleucel and lisocabtagene maraleucel. There was no difference in mean CRS grade, rate of ≥2 grade CRS, or in tocilizumab or steroids use between those with and without cardiac dysfunction. During a median follow-up of 294 (IQR 123-661) days, 60 (25%) patients experienced CV events with more events in patients with cardiac dysfunction (63% vs 21%, p&lt;0.001). In a Cox model adjusted for covariates identified in univariate analyses, baseline cardiac dysfunction was independently associated with an increased CV events risk (adjusted HR: 4.9, 95% CI 2.54–9.61, p&lt;0.001) Conclusions: CAR-T recipients with pre-existing cardiac dysfunction experience more CV events despite similar rates of CRS.
Abstract 11504: Elevated Seismocardiography-Derived Chest Energy is Associated With Aortic Flow Abnormalities in Patients With Aortic Valve Disease
Authors: Ethan M Johnson, Alexander J Barker, Joshua D Robinson, Cynthia K Rigsby, Michael Markl
Journal: Circulation (2022)

Introduction: Aortic valve disease (AVD) can induce abnormal flow and elevated peak velocity (Vmax), which has known association with aortopathy and implications for intervention, and thus is a key metric in AVD management. Seismocardiogram (SCG) chest acceleration measurements have been shown indicative of AVD. This study investigated relations between SCG energy and established aortic flow measures. Hypothesis: We hypothesize that standard of care clinical Vmax measurements from echocardiography or MRI correlate with SCG chest acceleration energy metrics. Methods: Healthy controls and AVD patients received standard of care echo or MRI and a same day SCG measurement (image, A). Patients had tricuspid or bicuspid aortic valve (TAV, BAV) and were presenting for routine imaging to assess valve/flow function (image, B). Controls (no known cardiovascular disease) were prospectively recruited. Subjects gave informed consent with IRB approval. MRI included 4D flow (1.5T, 1-3mm³/30-40ms); echo included 2D Doppler imaging (1.7-3.3MHz, 12-40 FPS). Standardized ascending aorta (AAo) Vmax measurements were taken from MR or echo images. SCG energy was calculated by spectral decomposition. Results: Enrolment was 76 subjects: 52 controls (48±17.4y, 23 F), 24 patients (18 BAV, 6 TAV, 31±20.9y, 5 F). Patients had elevated peak velocities (227±103cm/s vs. 106±21cm/s, p&lt;0.01) and elevated SCG energy (10.4±2.6dB vs. 8.3±1.4dB, p&lt;0.01). A significant relationship between elevated AAo Vmax and increased SCG energy was observed (R=0.63, p&lt;0.01) (image, C). Conclusions: Evaluation of SCG in context of AVD shows its potential utility to screen for valve mediated aortic flow changes. Correlation observed between SCG energy and peak velocities, a key metric for management of valve disease and aortopathy, indicates the relevance of SCG measurements in this context. These results show potential for use of SCG as simple, cost-effective front-line screening tool for AVD patients.
Abstract 12120: Association of Physical Activity and Myocardial Fibrosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ralph Zeitoun, Omar Chehab, Xiaoyang Ma, Mahsima Shabani, Vinithra Varadarajan, Colin O Wu, Roberta Florido, Wendy S Post, Robyn L McClelland, Steven Shea, David A Bluemke, Bharath Ambale-Venkatesh, Joao A Ac Lima
Journal: Circulation (2022)

Introduction: Extracellular volume (ECV), native T1 time and late gadolinium enhancement (LGE) are markers of myocardial fibrosis (MF) by cardiac magnetic resonance imaging (CMR), and are associated with CV events, HF and death. Population studies on the association of physical activity (PA) and MF have not been published. Methods: MESA participants with data on Moderate and Vigorous PA (MET*min/week) at Exams 1, 2, 3 or 5, and ECV (%), T1 time (ms) and presence of LGE at Exam 5 were included. We constructed participant-specific trajectories of log-transformed PA levels using nonparametric B-splines based on best linear unbiased prediction. The area under the trajectory curve was used to estimate the 10-year PA level prior to Exam 5. We explored the associations of log-transformed PA at Exam 1 (PA 1 ), at Exam 5 (PA 5 ) and cumulative over 10 years (PA 1-5 ), with outcomes of interest (ECV, T1 time and LGE), using multivariable analysis. PA values were divided by their respective SD. Covariates included were demographic and lifestyle factors, CVD risk factors and CVD events. Results: A total of 2,682 participants were included (52% women, mean age 69 ± 9 years). PA 1 , PA 5 , and PA 1-5 were significantly greater in men (p&lt;0.001 for all). PA 1 , PA 5 and PA 1-5 were not associated with ECV, T1 time or LGE in any model, for the entire cohort. Although interaction of PA 5 and PA 1-5 with sex was significant in the association with ECV, there was no significant association between PA and ECV in either men or women. Additionally, interaction of PA with sex was not significant in the association with either T1 time or LGE. Conclusions: In the MESA cohort, greater moderate and vigorous physical activity at baseline, at time of CMR, and cumulative over 10 years prior to CMR was not associated with ECV, native T1 time or LGE. Additionally, although interaction of PA with sex was significant in the association with ECV, there was no significant association between PA and ECV in either men or women.
Abstract 11386: Double Whammy Complicating Management of Pulmonary Hypertension
Authors: Ayesha Salahuddin, Khaled W Tuwairqi, Ian Harris, Anushree Agarwal, Vaikom Mahadevan, Peter Kouretas, Aarthi Sabanayagam
Journal: Circulation (2022)

Introduction: When presented with challenging cardiac cases, in addition to obvious diagnoses, it is critical to maintain high level of suspicion about other subtle conditions. We describe one such case of pulmonary arterial hypertension (PAH) from severe mitral stenosis (MS) and another less obvious congenital cardiac condition that significantly impacted the clinical course. Case: 32-year-old immigrant male with known heart murmur presented with palpitations due to atrial fibrillation. His resting oxygen saturation was 95% in all extremities and he had no clubbing. He had pectus carinatum and scoliosis, prominent right ventricular lift, normal S1, loud S2, opening snap, rumbling diastolic murmur at the apex, and an ejection systolic murmur at the left upper sternal border. Echocardiogram revealed normal biventricular size and function, severely enlarged left atrium, rheumatic severe MS, moderate mitral regurgitation, a restrictive ventricular septal defect (VSD), and elevated right ventricular systolic pressure. Cardiac catheterization demonstrated mixed pre- and post-capillary PAH with mean pulmonary artery pressure of 80 mmHg, wedge pressure 30 mm Hg and pulmonary vascular resistance of 3.0 woods unit which was underestimated. Since pre-capillary component of the PAH could not be entirely explained by the small VSD, a congenital cardiac CT was performed revealing moderate sized patent ductus arteriosus (PDA). Further management decisions were complicated since MS was not amenable to percutaneous intervention and surgical risks were high given severe pre-capillary PAH- management of which with pulmonary vasodilators was itself high risk in the setting of severe MS and high wedge pressures. After optimal medical management, a multidisciplinary team carefully considered the risks and benefits of multiple interventions. Ultimately, the patient underwent surgical mitral valve replacement, fenestrated patch closure of the PDA, and then initiation of pulmonary vasodilators. The patient continues to do well on oral pulmonary vasodilator therapy 6 months after surgery. Conclusion: We describe an astute critical thought process of a multidisciplinary team utilized to manage a challenging case of mixed PAH from severe rheumatic MS and PDA.
Abstract 12537: Iron Deficiency in Korean Patients With Heart Failure
Authors: MINJAE YOON, Dong Choi
Journal: Circulation (2022)

Introduction: Although iron deficiency (ID) is an important and treatable risk factor for heart failure (HF), data on ID are scarce in Asian patients with HF. Therefore, we sought to determine the prevalence and clinical characteristics of ID in hospitalized Korean patients with HF. Methods: In this prospective, multicenter cohort study, 461 patients with acute HF seen at five centers from January to November 2019 in Korea were enrolled. ID was defined as serum ferritin &lt;100 μg/L or ferritin 100-299 μg/L in combination with transferrin saturation &lt;20%. Results: The patients’ mean age was 67.6±14.9 years, and 61.8% were male. Overall, 53.8% had ID. In a multivariable logistic regression analysis, the independent predictors of ID were female sex (odds ratio [OR], 2.18; 91% confidence interval [CI], 1.46-3.26), higher heart rate (OR, 1.01; 95% CI, 1.00-1.02), anemia (OR, 1.80; 95% CI, 1.21-2.67), and the use of clopidogrel (OR, 1.67; 95% CI 1.07-2.06). Among women, the prevalence of ID did not differ between younger and older women (&lt;65 years: 73.7% vs. ≥65 years: 63.0%, P=0.222), those with low and high body mass index (BMI&lt;25 kg/m2: 66.2% vs. BMI≥25 kg/m2: 69.6%, P=0.703), and those with low and high natriuretic peptide (NP) levels (NP &lt;median: 69.8% vs. NP ≥median: 61.1%, P=0.295). Only 0.2% received intravenous iron supplementation. Conclusions: The prevalence of ID is high in hospitalized Korean patients with HF. Because ID cannot solely be diagnosed by clinical parameters, routine laboratory examinations are necessary to identify patients with ID. Efforts should be made to overcome the low use of intravenous iron supplementation in Korea.
Abstract 12311: The Impact of Ejection Fraction on Major Adverse Limb Events After Lower Extremity Revascularization
Authors: Yasser Jamil, Joshua Huttler, Dana Alameddine, Haoran Zhuo, Carlos Mena-Hurtado, Eric J Velazquez, Raul J Guzman, Cassius Iyad I Ochoa Chaar
Journal: Circulation (2022)

Objective: Peripheral arterial disease (PAD) is commonly associated with cardiac disease and echocardiography is frequently performed prior to lower extremity revascularization (LER). However, the incidence of various echocardiographic findings and their impact on the outcomes of LER have not been well studied. Hypothesis: Low ejection fraction (EF) ≤ 40% is associated with increased major adverse limb events (MALE) after LER. Methods: The electronic records of patients undergoing LER in a single center were reviewed. Patients were divided based on the presence or absence of reduced EF ≤ 40%. Patient, echocardiographic, and procedural characteristics were compared as well as outcomes. Results: A total of 1,034 patients (N=130, 12.5% with EF≤ 40%) underwent LER. Patients with reduced EF were more likely to be males, with coronary artery disease and heart failure. On echocardiography, patients with reduced EF had significantly higher mean right ventricular pressure and were more likely to have diastolic dysfunction. Moderate to severe regurgitation affecting the mitral and tricuspid valves were significantly higher in patients with reduced EF. There was no difference in indication but patients with reduced EF were more likely to be treated with endovascular procedures. Perioperatively, patients with reduced EF were more likely to develop myocardial infarction. (Table) There was no difference in MALE or major amputation between the 2 groups but MALE-free survival was significantly lower for patients with EF≤ 40%. (Figure). Conclusion: Reduced EF is associated with decreased survival of patients with PAD after LER but does not seem to significantly impact MALE.
Abstract 11889: Effectiveness of sST2-Guided Therapy in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Marina Muksinova, Oleg Narusov, Valeriy Masenko, Alexey Sychev, Sergey Tereschenko, Andrey Skvortsov
Journal: Circulation (2022)

Introduction: Natriuretic peptide-guided therapy has not proven to be more sufficiently effective than usual care (UC) in patients with heart failure (HF). Soluble ST2 (sST2) has a number of advantages over natriuretic peptides. Hypothesis: sST2-guided therapy (sST2-GT) will be more effective than UC in patients with HFrEF. Methods: The prospective study included 76 patients (pts) with HFrEF, who were hospitalized due to acute decompensated HF. Pts with sST2 levels ≥ 37.8 ng/ml at the time of discharge constituted the high-risk cohort and were randomized into 2 groups: 19 pts in the sST2-GT and 18 patients in the UC. 39 pts with sST2 &lt; 37.8 ng/ml and NT-proBNP &lt; 1700 pg/ml were included in the low-risk cohort. The duration of the active treatment period was 6 months with monthly visits for therapy correction, the total follow-up period was up to 1 year. Therapy was carried out in accordance with clinical recommendations. In the sST2-GT group, therapy was also adjusted taking into account the concentration of sST2. The goal in this group was to reduce sST2 concentration by more than 30% or to less than 30 ng/ml. Measurement of sST2 (ASPECT-PLUS) concentration, echocardiography and registration combined endpoints (CEP) (HF decompensation (HFD) or cardiovascular mortality) were identified in all groups after 6 and 12 months. Results: Pts therapy in both high-risk groups was comparable, but pts in the sST2-GT group had a greater number of study clinic visits (7.1±2.3 vs 5.6±1.6 (p=0.024) compared with UC group. Pts sST2 concentration decreased in both high-risk groups, with the study goal achieved in 68,4% of pts in sST-GT group. Fewer CEP were registered In sST2-GT group pts compared to the UC group (for 6 months - 5 (0.26 / pt) vs 15 (0.83 / pt), p = 0.029 and 9 (0.47/pt) vs 22 (1.22/pt), p=0.035 over the entire follow-up) and it was practically similar low-risk cohort (0.46/patient). Fewer HFD were registered in the sST2-GT group compared to the UC group (for 6 months 4 (0.21 /pt) vs 13 (0.72 /pt), p &lt; 0.001 and 8 (0.42/pt) vs 19 (1.06/pt), p&lt;0.001 over entire follow-up), which was similar the low-risk group (0,31/pt). LV EF increased only in the sST2-GT group (from 29.2±6.2 up to 36.1±8.8, p=0.003 for 6 months). Conclusions: sST2-GT in high-risk pts with HFrEF is more effective than UC.
Abstract 11554: Biochemical and Molecular Newborn Screening for Familial Hypercholesterolemia
Authors: Amy L Peterson, Patrice K Held, Xiangqiang Shao, Michael Lasarev, Xiao Zhang, Amy Wiberley-Bradford, Kristin Campbell, Megan Benoy, Ann M Dodge, Vanessa Horner
Journal: Circulation (2022)

Introduction: Familial Hypercholesterolemia (FH) is a common genetic disorder resulting in elevated low-density lipoprotein cholesterol (LDL-C) causing premature atherosclerosis. Despite guidelines, universal screening rates remain low. Newborn screening could increase FH diagnostic rates. Hypothesis: Biochemical newborn screening for LDL-C, total cholesterol (TC), and apolipoprotein B (apoB) followed by selective molecular testing identifies pathogenic and likely pathogenic variants causing FH. Methods: De-identified, residual newborn screening bloodspots collected for routine screening at 24-48 hours of life were analyzed for LDL-C, TC, and apoB. Values are expressed as multiples of median (MoM). Mahalanobis distance, measuring how far MoM values differed positively from 1, was computed. Samples with the most extreme Mahalanobis distance were selected for molecular testing (panel includes LDLR , APOB , PCSK9 , LDLRAP1 , APOE , STAP1 , LIPA , ABCG5 , and ABCG8 ). Results: Distributions of apoB, TC, and LDL-C from 5,248 samples are shown below (figure). ApoB followed a Gamma distribution; TC and LDL-C followed non-normal but symmetric distributions. ApoB and LDL-C accounted for 93% of variance among biomarkers. Of the first 2500 samples, 192 samples were selected for molecular testing; a pathogenic variant for monogenic FH was detected in 1 sample and risk factors for polygenic FH in 4 samples (table below). Conclusions: Pathogenic or likely pathogenic variants for FH were identified with an incidence of 1 in 500 in the first 2500 newborn specimens tested. Further study will determine if this two-tiered screening strategy adequately detects FH in newborns.
Abstract 11820: A Meta-Analysis of Efficacy and Safety of the New Generation Watchman FLX Device Compared to the Watchman 2.5
Authors: Mostafa R Zaalouk, Mohamed Eid, Ahmad Al-Abdouh, Mahmoud Ismayl, Sarah Mohamed, Sarath lal Mannumbeth renjithlal, Mahmood Mubasher, Mamas Mamas
Journal: Circulation (2022)

Introduction: The first-generation Watchman 2.5 (W2.5) is associated with several limitations, including the difficulty of implantation in complex LAA anatomies, peri device leak, device recapture and device-related thrombosis. The second-generation Watchman FLX (W-FLX) addressed those limitations with proven safety and efficacy of the device. Hypothesis: This meta-analysis compares the safety and efficacy of the Watchman FLX and 2.5 devices. Methods: The meta-analysis was conducted according to PRISMA guidelines. Studies were located through a search strategy utilizing PubMed, Google scholar and MEDLINE from inception to March 20, 2022, with a primary objective to compare the safety and efficacy of the W-FLX and W2.5. After setting inclusion and exclusion criteria, we identified three recently published observational studies. Results: Our analysis included 3 studies comprising 401 patients. New generation W- FLX is associated with less incidence of major-leak compared to the first-generation W 2.5, OR: 0.08 CI (0.06-0.12) P &lt;0.01 (Figure 1). There was no difference in mortality OR: 1.38 CI (0.00-152360) P .78, procedure success OR: 16.07 CI (0.06-4676.83) P 0.1 or post-procedural complications (Bleeding OR: 0.63 CI (0.03-13.07) P 0.31, device embolization OR: 0.12 CI (0.00-3.79) P 0.08, pericardial effusion OR: 0.14 CI (0.00-12.23) P 0.11 or stroke OR: 0.7 CI (0.00-9170) P 0.71) across the two devices. Conclusions: The new generation Watchman FLX has a superior sealing capacity than the Watchman 2.5 with a similar safety profile.
Abstract 11540: Dephospho-Uncarboxylated Matrix Gla-Protein and Adverse Outcomes in Heart Failure: A Mendelian Randomization Analysis
Authors: Mahesh K Vidula, Leon J Schurgers, Chenao Qian, Oday Salman, Qasim Jehangir, Jordana Cohen, Erika Kvikstad, Joseph Maranville, Lei Zhao, Ching-Pin Chang, David A Gordon, Francisco Ramirez-Valle, Tom Cappola, Julio A Chirinos
Journal: Circulation (2022)

Introduction: Matrix Gla-protein (MGP) is a known inhibitor of vascular calcification and is activated by vitamin K-dependent carboxylation. Carboxylation is reduced in vitamin K-deficient states, resulting in increased circulating dephospho-uncarboxylated MGP (dpucMGP). Elevated dpucMGP levels have been associated with large artery stiffenning and worse outcomes in heart failure (HF). We assessed the causal relationship between dpucMGP and adverse outcomes in human HF using Mendelian Randomization (MR). Methods: We measured dpucMGP among 2379 Penn Heart Failure Study (PHFS) participants and analyzed a subset with genotypic data (n=1334). We constructed a genetic risk score (GRS) using independent single nucleotide polymorphisms (SNPs) associated with dpucMGP levels at genome-wide significance, and utilized MR analysis to assess the association between genetically determined dpucMGP levels and 1) all-cause death, and 2) death or heart failure-related hospital admission (DHFA). Results: Measured dpucMGP levels were associated with an increased risk of death ( Figure 1A ) and DHFA ( Figure 1B ). DpucMGP levels were significantly associated with 55 genome-wide SNPs. MR analysis demonstrated a significant relationship between genetically determined dpucMGP and the risk of death (hazard ratio [HR] 1.67, P =0.013) and DHFA (HR 1.51, P =0.004). Conclusions: Elevated dpucMGP levels are associated with increased risk for all-cause death and DHFA in patients with heart failure, and this relationship is likely causal. Further studies are required to determine the role of vitamin K supplementation in this patient population.